Handheld gas analysis systems for point-of-care medical applications

ABSTRACT

The disclosure describes a substrate with a fluid-handling assembly coupled to the substrate, the fluid-handling assembly including a plurality of fluid-handling components removably coupled to the substrate and removably coupled to each other. The plurality of fluid handling components includes a gas chromatograph having a fluid inlet and a fluid outlet, and a detector array having a fluid inlet and a fluid outlet, wherein the fluid inlet of the detector array is fluidly coupled to the fluid outlet of the gas chromatograph. A control circuit is communicatively coupled to at least one of the plurality of fluid-handling components, and a readout circuit communicatively coupled to the detector array and to the control circuit. Other embodiments are disclosed and claimed.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.12/140,822, filed 17 Jun. 2008, and claims priority therefrom under 35U.S.C. §120. The priority application is currently pending.

TECHNICAL FIELD

The present invention relates generally to gas analysis systems and inparticular, but not exclusively, to handheld gas analysis systems forpoint-of-care medical applications.

BACKGROUND

Gas analysis can be an important means for detecting the presence andconcentration of certain chemicals in the gas and determining themeaning of the particular combination of chemicals present. In healthcare, for example, the presence of certain volatile organic compounds(VOCs) in exhaled human breath are correlated to certain diseases, suchas pneumonia, pulmonary tuberculosis (TB), asthma, lung cancer, liverdiseases, kidney diseases, etc. The correlations are especiallyevidential for lung-related diseases. In other applications, gasanalysis can be used to determine the presence of dangerous substancesincompatible with human presence, such as methane, carbon monoxide orcarbon dioxide in a mine.

Current gas analytical systems still rely heavily on large and expensivelaboratory instruments, such as gas chromatography (GC) and massspectrometry (MS). Most of these instruments (mass spectrometers inparticular) have operational characteristics that prevent significantreductions in their size, meaning that current gas analysis systems arelarge and expensive bench devices.

In addition to being expensive and unwieldy, the large size of currentgas analysis devices makes widespread use of these instrumentsimpossible.

BRIEF DESCRIPTION OF THE DRAWINGS

Non-limiting and non-exhaustive embodiments of the present invention aredescribed with reference to the following figures, wherein likereference numerals refer to like parts throughout the various viewsunless otherwise specified.

FIG. 1A is a side elevation drawing of an embodiment of a gas analysisdevice.

FIG. 1B is a plan view of the embodiment of a gas analysis device shownin FIG. 1.

FIG. 2 is a cross-sectional elevation drawing of an embodiment of a MEMSpre-concentrator that can be used in the embodiment of a gas analysisdevice shown in FIGS. 1A-1B.

FIG. 3A is a plan view drawing of an embodiment of a MEMS gaschromatograph that can be used in the embodiment of a gas analysisdevice shown in FIGS. 1A-1B

FIG. 3B is a cross-sectional elevation drawing of the embodiment of aMEMS gas chromatograph shown in FIG. 3A, taken substantially alongsection line B-B.

FIG. 4A is a plan view drawing of an embodiment of a detector array thatcan be used in the embodiment of a gas analysis device of FIGS. 1A-1B.

FIG. 4B is a cross-sectional elevation drawing of the embodiment of adetector array shown in FIG. 4A, taken substantially along section lineB-B.

FIG. 5 is a schematic diagram of an alternative embodiment of a gasanalysis device and an embodiment of a system using the embodiment ofthe gas analysis device.

FIG. 6 is a schematic diagram of another alternative embodiment of a gasanalysis device and an embodiment of a system using the embodiment ofthe gas analysis device.

FIG. 7 is a plan-view schematic diagram of an additional alternativeembodiment of a gas analysis device.

FIG. 8 is a plan-view schematic diagram of an additional alternativeembodiment of a gas analysis device.

FIG. 9 is a plan-view schematic diagram of an additional alternativeembodiment of a gas analysis device.

DETAILED DESCRIPTION OF THE ILLUSTRATED EMBODIMENTS

Embodiments of an apparatus, process and system for gas analysis inpoint-of-care medical applications are described herein. In thefollowing description, numerous specific details are described toprovide a thorough understanding of embodiments of the invention. Oneskilled in the relevant art will recognize, however, that the inventioncan be practiced without one or more of the specific details, or withother methods, components, materials, etc. In other instances,well-known structures, materials, or operations are not shown ordescribed in detail but are nonetheless encompassed within the scope ofthe invention.

Reference throughout this specification to “one embodiment” or “anembodiment” means that a particular feature, structure, orcharacteristic described in connection with the embodiment is includedin at least one embodiment of the present invention. Thus, appearancesof the phrases “in one embodiment” or “in an embodiment” in thisspecification do not necessarily all refer to the same embodiment.Furthermore, the particular features, structures, or characteristics maybe combined in any suitable manner in one or more embodiments.

FIGS. 1A and 1B together illustrate an embodiment of a small scale(e.g., handheld) gas analysis device 100. Device 100 includes asubstrate 102 on which are mounted a fluid handling assembly 101, acontroller 126 coupled to the individual elements within fluid handlingassembly 101, and a reading and analysis circuit 128 coupled to detectorarray 110 and to controller 126. The embodiment shown in the figuresillustrates one possible arrangement of the elements on substrate 102,but in other embodiments the elements can, of course, be arranged on thesubstrate differently.

Substrate 102 can be any kind of substrate that provides the requiredphysical support and communication connections for the elements ofdevice 100. In one embodiment, substrate 102 can be a printed circuitboard (PCB) of the single-layer variety with conductive traces on itssurface, but in other embodiments it can be a PCB of the multi-layervariety with conductive traces in the interior of the circuit board. Inother embodiments, for example an embodiment where device 100 is builtas a monolithic system on a single die, substrate 102 can be chip orwafer made of silicon or some other semiconductor. In still otherembodiments, substrate 102 can also be a chip or wafer in which opticalwaveguides can be formed to support optical communication between thecomponents of device 100.

Fluid handling assembly 101 includes a filter and valve assembly 104, apre-concentrator 106, a gas chromatograph 108, a detector array 110 anda pump 112. Elements 104-112 are fluidly coupled in series: filter andvalve assembly 104 is fluidly coupled to pre-concentrator 106 by fluidconnection 116, pre-concentrator 106 is fluidly coupled to gaschromatograph 108 by fluid connection 118, gas chromatograph 108 isfluidly coupled to detector array 110 by fluid connection 120, anddetector array 110 is coupled to pump 112 by fluid connection 122. Asfurther described below, in one embodiment of device 100 elements104-112 can be micro-electro-mechanical (MEMS) elements or MEMS-basedelements, meaning that some parts of each device can be MEMS and otherparts not. In other embodiments of device 100, some or all of elements104-112 need not be MEMS or MEMS-based, but can instead be some non-MEMSchip scale device.

As indicated by the arrows in the figures, the fluid connections betweenelements 104-112 allow a fluid (e.g., one or more gases) to enter filterand valve assembly 104 through inlet 114, flow though elements 104-112,and finally exit pump 112 through outlet 124. Fluid handling assembly101 also includes a shroud or cover 125 that protects individualelements 104-112. In the illustrated embodiment, channels formed inshroud 125 provide the fluid connections between the elements, but inother embodiments the fluid connections between elements can be providedby other means, such as tubing. In still other embodiments shroud 125can be omitted.

Filter and valve assembly 104 includes an inlet 114 and an outletcoupled to fluid connection 116 such that fluid exiting filter and valveassembly 104 flows into pre-concentrator 110. Filter and valve assembly104 includes a filter to remove particulates from fluid entering throughinlet 114. In embodiments of device 100 where one or more of elements104-112 is a MEMS element, the small scale of parts within the MEMSelements of device pre-concentrator means that fluid entering throughinlet 114 can be filtered to remove these particles so that theparticles do not enter the MEMS devices and either damage them or renderthem inoperative. In embodiments of device 100 that include no MEMScomponents or where fluid entering inlet 114 contains no particles, forinstance because it has been pre-filtered externally to device 100, thefilter portion of filter and valve assembly 104 can be omitted.

Filter and valve assembly 104 also includes a valve so that further flowthrough inlet 114 into fluid handling assembly 101 can be stopped oncesufficient fluid has passed through the device. Stopping further flowthrough inlet 114 prevents dilution of fluids that will flow out ofpre-concentrator 106 during later operation of device 100 (seedescription of operation below). In other embodiments, filter and valveassembly 104 can also include a de-humidifier to remove water vapor fromthe fluid entering through inlet 114, thus improving the accuracy andsensitivity of device 100.

Pre-concentrator 106 includes an inlet coupled to fluid connection 116and an outlet coupled to fluid connection 118. Pre-concentrator 106receives fluid from filter and valve assembly 104 through fluidconnection 116 and outputs fluid to gas chromatograph 108 through fluidconnection 118. As fluid flows through pre-concentrator 106, thepre-concentrator absorbs certain chemicals from the passing fluid, thusconcentrating those chemicals for later separation and detection. In oneembodiment of device 100 pre-concentrator 106 can be a MEMSpre-concentrator, but in other embodiments pre-concentrator 106 can be anon-MEMS chip scale device. Further details of an embodiment of a MEMSpre-concentrator are described below in connection with FIG. 2.

Gas chromatograph 108 includes an inlet coupled to fluid connection 118and an outlet coupled to fluid connection 120. Gas chromatograph 108receives fluid from pre-concentrator 106 through fluid connection 118and outputs fluid to detector array 110 through fluid connection 120. Asfluid received from pre-concentrator 106 flows through gas chromatograph108, individual chemicals in the fluid received from thepre-concentrator are separated from each other in the time domain forlater input into detector array 110. In one embodiment of device 100 gaschromatograph 108 can be a MEMS gas chromatograph, but in otherembodiments gas chromatograph 108 can be a non-MEMS chip scale device.Further details of an embodiment of a MEMS gas chromatograph 108 aredescribed below in connection with FIGS. 3A-3B.

Detector array 110 includes an inlet coupled to fluid connection 120 andan outlet coupled fluid connection 122. Detector array 110 receivesfluid from gas chromatograph 108 through fluid connection 120 andoutputs fluid to pump 112 through fluid connection 122. As fluid flowsthrough detector array 110, the chemicals that were time-domainseparated by gas chromatograph 108 enter the detector array and theirpresence and/or concentration is sensed by sensors within the detectorarray. In one embodiment of device 100 detector array 110 can be a MEMSdetector array, but in other embodiments detector array 110 can be anon-MEMS chip scale device. Further details of an embodiment of adetector array 110 are described below in connection with FIG. 4.

Pump 112 includes an inlet coupled to fluid connection 122, as well asan outlet coupled to an exhaust 124, such that pump 112 draws fluid fromdetector array 110 through fluid connections 122 and returns it to theatmosphere through exhaust 124. Pump 112 can be any kind of pump thatmeets the size and form factor requirements of device 100, provides thedesired flow rate and flow rate control, and has adequate reliability(i.e., an adequate mean time between failures (MTBF)). In oneembodiment, pump 112 can be a MEMS or MEMS-based pump, but in otherembodiments it can be another type of pump. Examples of pumps that canbe used include small axial pumps (e.g., fans), piston pumps, andelectro-osmotic pumps.

Controller 126 is communicatively coupled to the individual elementswithin fluid handling assembly 101 such that it can send control signalsand/or receive feedback signals from the individual elements. In oneembodiment, controller 126 can be an application-specific integratedcircuit (ASIC) designed specifically for the task, for example a CMOScontroller including processing, volatile and/or non-volatile storage,memory and communication circuits, as well as associated logic tocontrol the various circuits and communicate externally to the elementsof fluid handling assembly 101. In other embodiments, however,controller 126 can instead be a general-purpose microprocessor in whichthe control functions are implemented in software. In the illustratedembodiment controller 126 is electrically coupled to the individualelements within fluid handling assembly 101 by conductive traces 130 onthe surface or in the interior of substrate 102, but in otherembodiments controller 126 can be coupled to the elements by othermeans, such as optical.

Readout and analysis circuit 128 is coupled to an output of detectorarray 110 such that it can receive data signals from individual sensorswithin detector array 110 and process and analyze these data signals. Inone embodiment, readout and analysis circuit 128 can be anapplication-specific integrated circuit (ASIC) designed specifically forthe task, such as a CMOS controller including processing, volatileand/or non-volatile storage, memory and communication circuits, as wellas associated logic to control the various circuits and communicateexternally. In other embodiments, however, readout and analysis circuit128 can instead be a general-purpose microprocessor in which the controlfunctions are implemented in software. In some embodiments readout andanalysis circuit 128 can also include signal conditioning and processingelements such as amplifiers, filters, analog-to-digital converters,etc., for both pre-processing of data signals received from detectorarray 110 and post-processing of data generated or extracted from thereceived data by readout and analysis circuit 128.

In the illustrated embodiment, readout and analysis circuit 128 iselectrically coupled to detector array 110 by conductive traces 132positioned on the surface or in the interior of substrate 102, but inother embodiments controller 126 can be coupled to the elements by othermeans, such as optical means. Readout and analysis circuit 128 is alsocoupled to controller 126 and can send signals to, and receive signalsfrom, controller 126 so that the two elements can coordinate andoptimize operation of device 100. Although the illustrated embodimentshows controller 126 and readout and analysis circuit 128 as physicallyseparate units, in other embodiments the controller and the readout andanalysis circuit could be combined in a single unit.

In operation of device 100, the system is first powered up and anynecessary logic (i.e., software instructions) is loaded into controller126 and readout and analysis circuit 128and initialized. Afterinitialization, the valve in filter and valve unit 104 is opened andpump 112 is set to allow flow through the fluid handling assembly. Fluidis then input to fluid handling assembly 101 through inlet 114 at acertain flow rate and/or for a certain amount of time; the amount oftime needed will usually be determined by the time needed forpre-concentrator 106 to generate adequate concentrations of theparticular chemicals whose presence and/or concentration are beingdetermined. As fluid is input to the system through inlet 114, it isfiltered by filter and valve assembly 104 and flows through elements104-112 within fluid handling assembly 101 by virtue of the fluidconnections between these elements. After flowing through elements104-112, the fluid exits the fluid handling assembly through exhaust124.

After the needed amount of fluid has been input through inlet 114, thevalve in filter and valve assembly 104 is closed to prevent furtherinput of fluid. After the valve is closed, a heater in pre-concentrator106 activates to heat the pre-concentrator. The heat releases thechemicals absorbed and concentrated by the pre-concentrator. As thechemicals are released from pre-concentrator 106, pump 112 is activatedto draw the released chemicals through gas chromatograph 108 anddetector array 110 and output the chemicals through exhaust 124.Activation of pump 112 also prevents backflow through fluid handlingassembly 101.

As the chemicals released from pre-concentrator 106 are drawn by pump112 through gas chromatograph 108, the chromatograph separates differentchemicals from each other in the time domain—that is, differentchemicals are output from the gas chromatograph at different times. Asthe different chemicals exit gas chromatograph 108 separated in time,each chemical enters MEMS detection array 110, where sensors in thedetection array detect the presence and/or concentration of eachchemical. The time-domain separation performed in gas chromatograph 108substantially enhances the accuracy and sensitivity of MEMS detectionarray 110, since it prevents numerous chemicals from entering thedetection array at the same time and thus prevents cross-contaminationand potential interference in the sensors within the array.

As individual sensors within MEMS detection array 110 interact with theentering time-domain-separated chemicals, the detection array senses theinteraction and outputs a signal to readout and analysis circuit 128,which can then use the signal to determine presence and/or concentrationof the chemicals. When readout and analysis circuit 128 has determinedthe presence and/or concentration of all the chemicals of interest itcan use various analysis techniques, such as correlation and patternmatching, to extract some meaning from the particular combination ofchemicals present and their concentrations.

FIG. 2 illustrates an embodiment of a MEMS pre-concentrator 200 that canbe used as pre-concentrator 106 in device 100. Pre-concentrator 200includes a substrate 202 having a cover plate 204 bonded thereto andsealed around the perimeter of the substrate to create a cavity 206.Substrate 202 has formed therein an inlet 208 on one side, an outlet 210on a different side, and pockets 212 having absorbents therein. In oneembodiment, substrate 202 is a silicon substrate, but in otherembodiments substrate 202 can of course be made of other materials.Heater 216 is formed on the side of substrate 202 opposite the sidewhere cover plate 204 is attached.

In an embodiment where substrate 202 is silicon, inlet 208, outlet 210and pockets 212 can be formed using standard photolithographicpatterning and etching. Although the illustrated embodiment shows sevenpockets 212 a-212 g, the number of pockets needed depends on the numberof different chemicals to be absorbed and concentrated, and on thenature of the absorbents used. In an embodiment where each absorbentabsorbs only one chemical, the number of pockets 212 can correspondexactly to the number of chemicals to be absorbed and concentrated, butin other embodiments where each absorbent absorbs only one chemical agreater number of pockets can be used to increase the absorption area.In still other embodiments where each absorbent can absorb more than onechemical, a lesser number of pockets can be used.

Each pocket 212 has a corresponding absorbent 214 in its interior—pocket212 a has absorbent 214 a, pocket 212 b has absorbent 214 b, and so on.Although shown in the illustrated embodiment as a granular absorbent, inother embodiments absorbents 214 can be coatings on the walls of pockets212 or can be a continuous substance that partially or fully fills eachpocket 212. Other embodiments can include combinations of granular, wallcoatings or continuous filling absorbents. Each absorbent can have achemical affinity for one or more particular chemicals, meaning that theexact absorbents used will depend on the number and nature of chemicalsto be absorbed and concentrated. Examples of absorbents that can be usedinclude cabopack B, cabopack X, etc.

During operation of MEMS pre-concentrator 200 in device 100, fluid fromfilter and valve assembly 104 enters through inlet 208, passes throughabsorbent 214 a in pocket 212 a, and enters cavity 206. Cover plate 204helps guide fluid entering the cavity 206 into the different pockets 212b-212 g and through absorbents 214 b-214 g, until the fluid, minus thechemicals absorbed by absorbents 214 a-214 g, exits the pre-concentratorthrough outlet 210. Once enough fluid has flowed through thepre-concentrator, the valve in filter and valve assembly 104 is closedto prevent further flow through inlet 208. Heater 216 is then activated.Heater 216 heats absorbents 214 a-214 f, causing them to release theabsorbed chemicals through processes such as outgassing. Simultaneouslywith activating heater 216, or shortly thereafter, pump 112 isactivated, drawing the released chemicals out through outlet 210 to gaschromatograph 108.

FIGS. 3A-3B illustrate an embodiment of a MEMS gas chromatograph 300that can be used as gas chromatograph 108 in device 100. MEMS gaschromatograph 300 includes a substrate 302 with an inlet 306 on oneside, an outlet 308 on a different side, and a separation column 310having a stationary phase coating on its walls. A cover plate 304 isbonded to substrate 302 to seal column 310. In one embodiment substrate302 is a silicon substrate, but in other embodiments substrate 302 canof course be made of other materials. In an embodiment where substrate302 is silicon, inlet 306, outlet 308 and column 310 can be formed usingstandard photolithographic patterning and etching, such as deep reactiveion etching (DRIE). Heater 314 is formed on the side of substrate 302opposite the side where cover plate 204 is attached.

Column 310 provides a continuous fluid path from inlet 306 to outlet308, and some or all of the walls of column 310 are coated with astationary phase coating that can interact with the chemicals beingseparated by the chromatograph. How thoroughly and how fast chemicalsare separated from the fluid depend on the stationary phase coating, theoverall path length of column 310, and the temperature. For a givenstationary phase coating, the longer the column the better the chemicalspectrum separation, but a long column also extends the separation time.For a given application, the required path length will therefore usuallybe determined by a tradeoff among the coating, the column length and thetemperature. The illustrated embodiment shows column 310 as a spiralcolumn in which the column path length will depend on the number ofcoils in the spiral. In other embodiments, however, column 310 can beshaped differently.

During operation of MEMS gas chromatograph 300 in device 100, fluid frompre-concentrator 106 enters through inlet 306 and passes through column310. As fluid passes through the column 310, the different chemicals inthe fluid interact with stationary phase coating 312 at different rates,meaning that the chemicals are separated after traveling through thecolumn, with the chemicals that interact strongly with the stationaryphase being separated first and the chemicals that interact weakly withthe stationary phase being separated last. In other words, chemicalsthat interact strongly with the stationary phase are retained longer inthe stationary phase, while chemicals that interacted weakly with thestationary phase retained less time in the stationary phase. In someembodiments of gas chromatograph 300 this time-domain separation canoccur according to molecular weight (e.g., chemicals with the lowestmolecular weight are separated first, followed by higher molecularweights), but in other embodiments it can occur according to otherchemical characteristics or other separation mechanisms. As thechemicals are time-domain separated, pump 112 draws them out of MEMS gaschromatograph 300 through outlet 308. Generally, the chemicals exitthrough outlet 308 in the reverse order of their separation—that is,chemicals with low retention time exit first, while chemicals withhigher retention times exit later. After leaving outlet 308, thechemicals enter detector array 110.

FIGS. 4A-4B illustrate an embodiment of a detector array 400 that can beused as detector array 110 in device 100. Detector array 400 includes asubstrate 402 with an array of sensors S1-S9 formed thereon. In theillustrated embodiment sensors S1-S9 form a regularly shaped 3-by-3array of sensors, but in other embodiments the sensor array can have agreater or lesser number of sensors, and the sensors can be arranged inany pattern, regular or irregular.

A cover 404 is bonded to the perimeter of substrate 402 to form a cavity410 within which sensors S1-S9 are located. Cover 404 also includes aninlet 406 through which fluid can enter from gas chromatograph 108 andan outlet 408 through which fluid can exit to pump 112. A heater 412 isformed on the side of substrate 402 opposite the side where cover 404 isattached to control the temperature of detector array 400, and hence thesensors within the detector array, during operation. Although not shownin the figure, detector array 400 of course includes outputs by whichsignals generated by sensors S1-S9 can be output for processing.

Each sensor S1-S9 includes a surface with a coating thereon. Eachcoating used will have an affinity for one or more of the particularchemicals being detected, such that the coating absorbs or chemicallyinteracts with its corresponding chemical or chemicals. The interactionbetween coating and chemical in turn changes a physical property of thesensor such as resonant frequency, capacitance or electrical resistance,and that changed physical property of the sensor can be measured using atransducer or other measurement device. The particular coatings chosenfor sensors S1-S9 will depend on the chemicals that sensor array 110will be used to detect. The chemical affinity of coatings also variesstrongly with temperature, so that the operating temperature rangeshould be considered in selecting coatings. In an embodiment wheresensor array 110 will be used to detect volatile organic compounds inhuman breath—such as benzene, toluene, n-octane, ethylbenzene,m,p-xylene, a-pinene, d-limonene, nonanal, and benzaldehyde,2-methylhexane, 4-methyloctane, and so on—coatings that can be used indifferent applications include amorphous copolymers of2,2-bistrifluoromethyl-4,5-difluoro-1,3-dioxole (PDD) andtetrafluoroethylene (TFE), PtC12 (olefin), C8-MPN, etc.

Although the illustrated embodiment has nine sensors, the number ofsensors needed depends on the number of different chemicals to bedetected, and on the nature of the coatings used on the sensors. In anembodiment where each coating absorbs or chemically interacts with onlyone chemical the number of sensors can correspond exactly to the numberof chemicals to be detected, but in other embodiments it can bedesirable to have a given coating on more than one sensor forredundancy. In most cases, however, there is no one-to-one correlationbetween chemicals to coatings; in other words, each coating reacts withmore than one different chemical and the reaction between differentchemicals and a given coating will vary in nature and strength. Adetector array having sensors with different coatings is thereforeuseful because the response of the detector array can have differentpatterns for different gases.

In one embodiment of sensor array 400, sensors S1-S9 are MEMS sensorspositioned on the surface of substrate 402, meaning that they aresurface micromachined sensors. In other embodiments using MEMS sensors,however, sensors S1-S9 can be bulk micromachined sensors, meaning thatat least some of the MEMS sensors are formed within substrate 402instead of on the surface. Still other embodiments of sensor array 110using MEMS sensors can include combinations of surface-micromachined andbulk-micromachined sensors.

Different types of MEMS sensors can be used, depending on theapplication and the required sensitivity. Examples of MEMS sensors thatcan be used include chemiresistors, bulk acoustic wave (BAW) sensors,etc. In other embodiments of detector array 400, one or more of sensorsS1-S9 can be a non-MEMS sensor. Examples of non-MEMS sensors that can beused in detector array 400 include SAW (surface acoustic wave) sensorswith quartz or Gallium Arsenide (GaAs) substrates.

During operation of MEMS detector array 400 in device 100, fluid fromgas chromatograph 108 enters through inlet 406 and passes into cavity410. Fluid entering cavity 410 carries time-domain separated chemicals.

As each chemical enters cavity 410 it interacts with one or more sensorswhose coating has an affinity for that chemical. The interaction of thechemical with the sensor is sensed and measured, and the presence andconcentration of the particular chemical can be extracted. As more fluidflows into cavity 410, the first chemical is pushed out of cavity 410through outlet 408 and fluid with the next time-domain-separatedchemical enters cavity 410, interacts with the sensor array and ismeasured. This process continues until all the time-domain-separatedchemicals from gas chromatograph 108 have flowed through detector array110. In some embodiments where the affinity of the coatings for theirchemicals is not strong, detector array 110 can be re-usable: after alltime-domain-separated chemicals have been sensed, heater 412 can beactivated to heat the sensors and cause the coatings to release therespective chemicals with which they interacted, making the interactionreversible. In embodiments where the affinity of each coating for itschemicals could be strong, heating of the sensor array could helprelease the partially absorbed gas from the coating materials.

FIG. 5 illustrates an embodiment of a system 500 using an alternativeembodiment of a MEMS-based gas analysis device 502. Device 502 is inmost respects similar to device 100. The primary difference betweendevice 502 and device 100 is the presence in device 502 of a wirelesstransceiver circuit 504 and an antenna 506 mounted on substrate 102.Wireless transceiver circuit 504 can both transmit (Tx) data and receive(Rx) data and is coupled to reading and analysis circuit 128 and antenna506.

In one embodiment of system 500, transceiver 504 can be used towirelessly transmit raw data from reading and analysis circuit 128 toone or both of a router 508 and a computer 510. When transmitted torouter 508, the data can then be re-transmitted to another destinationfor analysis. For example, in an application where device 502 is usedfor health-related chemical analysis, data sent to router 508 can bere-transmitted to one or more of a doctor's office, a hospital, agovernment health department, or someplace else for analysis andinterpretation. After analysis is complete, or if there is a problemwith the data, the doctor's office, hospital or health department cansend instructions to device 502 through router 508, antenna 506 andtransceiver 504 to signal the result, to try to fix or improve the data,or to signal that the test must be performed again.

Continuing with the same health-care example, in the same or anotherembodiment of system 500, wireless transceiver 504 can be used totransmit raw data to computer 510. Computer 510 can either forward theraw data to a doctor, hospital, etc., as did the router, or can analyzethe data with software installed thereon to provide extract informationfrom the data, such as one or more possible medical diagnoses, andprovide the extracted information to the user of device 502. When itprovides analysis and medical diagnoses, computer 510 can also forwardthe diagnosis, alone or with the analysis and raw data, on to thedoctor, hospital, etc. As with the router, the doctor's office, hospitalor health department can send instructions to device 502 throughcomputer 510, antenna 506 and transceiver 504 to try to fix or improvethe data, to signal that the test must be performed again, and so on.

Again continuing with the same health-care example, in still anotherembodiment of system 500 the raw data can be processed, and informationsuch as potential diagnoses extracted from the data, by reading andanalysis circuit 128. The potential diagnoses determined by reading andanalysis circuit 128 can then be sent to computer 510 to be reviewed bythe user and/or forwarded, or can be immediately forwarded alone or withthe supporting raw data to the doctor's office, etc.

FIG. 6 illustrates an embodiment of a system 600 using an alternativeembodiment of a MEMS-based gas analysis device 602. Device 602 is inmost respects similar to device 502. The primary difference betweendevice 502 and device 602 is that the wireless transceiver circuit 504and antenna 506 are replaced with a hardware data interface 604 coupledto reading and analysis circuit 128. In one embodiment, hardware datainterface 604 could be a network interface card, but in otherembodiments hardware data interface can be an Ethernet card, a simplecable plug, etc. External devices can be connected to device 602 throughtraditional means such as cables. Although it has a differentcommunication interface, device 602 and system 600 have all the samefunctionality as device 502 and system 500. As with system 500, insystem 600 MEMS-based gas analysis device 602 can transmit data to, andreceive data from, one or both of a computer 608 and a wireless device606, such as a cell phone or personal digital assistant (PDA). Whentransmitted to wireless device 606 the data can then be forwarded to adoctor's office, hospital, or government health department, and therecipients of the data can in turn send data or instructions back to gasanalysis device 602 through the wireless device. As in system 500, whendata is transmitted to computer 608 it can be forwarded or can beanalyzed by the computer and the result displayed for the user and/orforwarded, and instructions can be transmitted to device 602 throughcomputer 608. Similarly, the data from gas analysis device 602 can beanalyzed by reading and analysis circuit 128. After analysis by circuit128, the extracted information (e.g., one or more diagnoses) and/or theraw data can be forwarded via the hardware data interface 604.

FIG. 7 illustrates an alternative embodiment of a MEMS-based gasanalysis device 700. Device 700 is in most respects similar to device100. The primary difference between system 700 and device 100 is thatdevice 700 includes an on-board display 702 for conveying to a user theresults of the analysis performed by reading and analysis circuit 128.

The illustrated embodiment uses an on-board text display 702, forexample an LCD screen that can convey text information to a user. Forexample, in a health care example display 702 could be used to displaythe test results in analog numbers indicating the situation of patients.Display 702 could indicate a positive or negative diagnosis, couldindicate probabilities of a given diagnosis, or could indicate the rawdata from the detector array. In another health care embodiment, simplerdisplays can be used, such as one with three lights that indicate apositive, negative, or indeterminate result depending on which light isswitched on.

FIG. 8 illustrates an alternative embodiment of a MEMS-based gasanalysis device 800. Device 800 is in most respects similar to device100. The primary difference between device 800 and device 100 is that indevice 800 one or more elements of fluid handling assembly 101 arereplaceable.

In the illustrated embodiment, the elements are made replaceable bymounting them onto substrate 102 using sockets: filter and valveassembly 104 is mounted to substrate 102 by socket 804, pre-concentratoris mounted to substrate 102 by socket 804, gas chromatograph 108 ismounted to substrate 102 by socket 808, detector array 110 is mounted tosubstrate 102 by socket 810, and pump 112 is mounted to substrate 102 bysocket 812. In one embodiment, sockets 804-812 are sockets such as zeroinsertion force (ZIF) sockets that permit easy replacement by a user,but in other embodiments other types of sockets can be used. Althoughthe illustrated embodiment shows all the components of fluid handlingassembly 101 being replaceable, in other embodiments only some of thecomponents such as pump 112 and detector array 110 can be madereplaceable.

FIG. 9 illustrates an alternative embodiment of a MEMS-based gasanalysis device 900. Gas analysis device 900 is in most respects similarto device 100. The primary difference between device 900 and device 100is that device 900 includes provisions for an external pre-concentrator902 (i.e., a pre-concentrator not mounted on substrate 102). In theembodiment shown, a valve 904 is placed between pre-concentrator 106 andgas chromatograph 108, and provisions are made to attach externalpre-concentrator 902 to the valve. Valve 904 allows the user to useexternal pre-concentrator 902 instead of, or in addition to, on-boardpre-concentrator 106. In one embodiment external pre-concentrator 902 isa breath collection bag, but in other embodiments it can be somethingdifferent. In an alternative embodiment of device 900 (not shown),pre-concentrator 106 can be permanently removed and replaced by externalpre-concentrator 902. In another embodiment where externalpre-concentrator 902 replaces pre-concentrator 106, instead of insertinga valve between pre-concentrator 106 and gas chromatograph 108, externalpre-concentrator 902 can be coupled upstream of the filter and valveassembly 104.

Device Applications

Pre-clinical studies on human breath analysis have found that certainvolatile organic compounds (VOCs) of exhaled human breath are correlatedto certain diseases, such as pneumonia, pulmonary tuberculosis (TB),asthma, lung cancer, liver diseases, kidney diseases, etc. Thecorrelations are especially evidential for lung-related diseases.Current analytical systems still rely on large and expensive laboratoryinstruments, such as gas chromatography (GC) and mass spectrometry (MS).Mass spectrometers in particular are impossible to miniaturize, makingwidespread use of these diagnostic instruments impossible.

The embodiments of MEMS-based gas analysis sensors discussed aboveprovide a solution to this problem, and in particular could be usedadvantageously to diagnose and monitor various diseases such as asthma,lung cancer, lung-related diseases, and other non-lung diseases such askidney and liver diseases, and etc.

Asthma

Asthma is a chronic disease; therefore, regularly monitoring patient'sstatus is helpful to doctor on tracking patient's healing progresses.Therefore, the new idea of handheld diagnostics would make the breathanalysis possible done at home or anywhere. In current diagnostics thebasic measurement is peak flow rate and the following diagnosticcriteria are used by the British Thoracic Society, but the peak flowrate is a physical quantity measurement. Breath analysis could providespecific root causes of the bronchi contraction by measuring the VOCsfrom patient's breath. Embodiments of the MEMS-based gas analysissystems could be used to monitor the efficacy of the medication.Furthermore, the medication therapy can be tailored to individualpatient through this active monitoring by using this home-based device.

Tuberculosis

One third of the world's current population has been infected by TB. And75% of the cases are pulmonary TB. The infected rate in the developingcountries is much higher than developed countries. Therefore, there areurgent needs of developing affordable diagnostic devices for developingcountries. Embodiments of the MEMS-based gas analysis system wouldprovide a cost-effective solution. Tuberculosis is caused byMycobacterium. Current diagnostic is time consuming and difficult sinceculturing the slow growing Mycobacterium takes about 6 weeks. Therefore,a complete medical evaluation, including chest X-ray, Tuberculosisradiology, tuberculin skin test, microbiological smears and cultures, isused to get more accurate assessment. Therefore, the rapid diagnostic isvery valuable and our breath analysis approach could achieve such needs.

Lung Cancer

With early detection and treatment, the 5-year survival rate for lungcancer improves dramatically. Current diagnostic methods, such as chestX-ray and CT (computed tomography) scan, are difficult to detect earlystage lung cancer. Breath analysis using embodiments of the MEMS-basedgas analysis system could diagnose the early stage lung cancer.

Classification of Lung-Related Diseases with Similar Symptoms

Breath analysis on exhaled VOCs is viable method to identify patient'slung-related diseases, which has similar symptoms. For example,embodiments of the MEMS-based gas analysis system can provide the testeddata to medical doctors to classify which disease between cool,lung-cancer, or pneumonia the patient would have. Breath analysis wouldbe the first screening test because of its simplicity before going formore tedious diagnostic measurements.

The above description of illustrated embodiments of the invention,including what is described in the abstract, is not intended to beexhaustive or to limit the invention to the precise forms disclosed.While specific embodiments of, and examples for, the invention aredescribed herein for illustrative purposes, various equivalentmodifications are possible within the scope of the invention, as thoseskilled in the relevant art will recognize. These modifications can bemade to the invention in light of the above detailed description.

The terms used in the following claims should not be construed to limitthe invention to the specific embodiments disclosed in the specificationand the claims. Rather, the scope of the invention is to be determinedentirely by the following claims, which are to be construed inaccordance with established doctrines of claim interpretation.

1. An apparatus comprising: a substrate; a fluid-handling assemblycoupled to the substrate, the fluid-handling assembly including aplurality of fluid-handling components removably coupled to thesubstrate and removably coupled to each other, the plurality of fluidhandling components including: a gas chromatograph having a fluid inletand a fluid outlet, and a detector array having a fluid inlet and afluid outlet, wherein the fluid inlet of the detector array is fluidlycoupled to the fluid outlet of the gas chromatograph; a control circuitcommunicatively coupled to at least one of the plurality offluid-handling components; and a readout circuit communicatively coupledto the detector array and to the control circuit.
 2. The apparatus ofclaim 1 wherein the readout circuit includes an analysis circuit andassociated logic to analyze an output signal received from the detectorarray.
 3. The apparatus of claim 2, further comprising an indicatorcoupled to an output of the analysis circuit to indicate to a user aresult of the analysis.
 4. The apparatus of claim 1 wherein theplurality of fluid-handling components further comprises apre-concentrator having a fluid inlet and a fluid outlet, wherein thepre-concentrator is removably coupled to the control circuit and whereinthe fluid outlet of the pre-concentrator is removably coupled to thefluid inlet of the gas chromatograph.
 5. The apparatus of claim 4wherein the plurality of fluid-handling components further comprises afilter and valve unit having a fluid inlet and a fluid outlet, whereinthe filter and valve unit is removably coupled to the control circuitand wherein the fluid outlet of the filter and valve unit is removablycoupled to the fluid inlet of the pre-concentrator.
 6. The apparatus ofclaim 5 wherein the plurality of fluid-handling components furthercomprises a pump having a fluid inlet and a fluid outlet, wherein thepump is removably coupled to the control circuit and wherein the fluidinlet of the pump is removably coupled to the fluid outlet of thedetector array.
 7. The apparatus of claim 6 wherein fluid-handlingassembly further comprises a shroud covering the plurality offluid-handling components.
 8. The apparatus of claim 7 wherein theshroud provides the removable coupling among the plurality offluid-handling components.
 9. The apparatus of claim 5 wherein fluidcouplings provide the removable coupling among the plurality offluid-handling components.
 10. The apparatus of claim 1 wherein thesubstrate is a printed circuit board that includes electricalconnections that communicatively couple the control circuit to one ormore of the plurality of fluid-handling components and the readoutcircuit to the detector array.
 11. The apparatus of claim 1 wherein thedetector array includes one or more MEMS detectors, wherein at least oneof the one or more MEMS detectors can be a chemiresistor or a bulkacoustic wave sensor.
 12. The apparatus of claim 1 wherein the detectorarray includes one or more non-MEMS detectors, wherein at least one ofthe one or more non-MEMS detectors can be a surface acoustic wavesensor.
 13. A system comprising: a gas analysis device comprising: asubstrate; a fluid-handling assembly coupled to the substrate, thefluid-handling assembly including a plurality of fluid-handlingcomponents removably coupled to the substrate and removably coupled toeach other, the plurality of fluid handling components including: a gaschromatograph having a fluid inlet and a fluid outlet, and a detectorarray having a fluid inlet and a fluid outlet, wherein the fluid inletof the detector array is fluidly coupled to the fluid outlet of the gaschromatograph; a control circuit communicatively coupled to at least oneof the plurality of fluid-handling components; a readout circuitcommunicatively coupled to the detector array and to the controlcircuit; and a communication interface coupled to the readout circuit.14. The system of claim 13, further comprising a pre-concentrator havinga fluid inlet and a fluid outlet, wherein the pre-concentrator isremovably coupled to the control circuit and wherein the fluid outlet ofthe pre-concentrator is removably coupled to the fluid inlet of the gaschromatograph.
 15. The system of claim 14, further comprising a filterand valve unit having a fluid inlet and a fluid outlet, wherein thefilter and valve unit is removably coupled to the control circuit andwherein the fluid outlet of the filter and valve unit is removablycoupled to the fluid inlet of the pre-concentrator.
 16. The system ofclaim 15, further comprising a pump having a fluid inlet and a fluidoutlet, wherein the pump is removably coupled to the control circuit andwherein the fluid inlet of the pump is removably coupled to the fluidoutlet of the detector array.
 17. The system of claim 13 wherein thereadout circuit includes an analysis circuit and associated logic toanalyze the output signals received from the detector array.
 18. Thesystem of claim 13 wherein the communication interface comprises awireless transceiver mounted on the substrate and an antenna mounted tothe substrate and coupled to the wireless transceiver.
 19. The system ofclaim 18, further comprising one or both of a router and a computer withwhich the gas analysis device can communicate through the wirelesstransceiver and the antenna.
 20. The system of claim 13 wherein thecommunication interface comprises a hardware data interface.
 21. Thesystem of claim 20, further comprising one or both of a wireless deviceand a computer with which the gas analysis device can communicatethrough the hardware data interface.
 22. An apparatus comprising: asubstrate; a fluid-handling assembly coupled to the substrate, thefluid-handling assembly including a plurality of fluid-handlingcomponents removably coupled to the substrate and removably coupled toeach other, the plurality of fluid handling components including: a gaschromatograph having a fluid inlet and a fluid outlet, apre-concentrator having a fluid inlet and a fluid outlet, wherein thefluid outlet of the pre-concentrator is coupled to the fluid inlet ofthe gas chromatograph, and a detector array having a fluid inlet and afluid outlet, wherein the fluid inlet of the detector array is fluidlycoupled to the fluid outlet of the gas chromatograph; an externalpre-concentrator having a fluid outlet coupled to the fluid couplingbetween the outlet of the pre-concentrator and the inlet of the gaschromatograph; a control circuit communicatively coupled to at least oneof the plurality of fluid-handling components; and a readout circuitcommunicatively coupled to the detector array and to the controlcircuit.
 23. The apparatus of claim 22, further comprising a three-wayvalve removably coupled to the fluid outlet of the pre-concentrator, tothe fluid inlet of the gas chromatograph, and to the fluid outlet of theexternal pre-concentrator.
 24. The apparatus of claim 22 wherein thereadout circuit includes thereon an analysis circuit and associatedlogic to analyze an output signal received from the detector array. 25.The apparatus of claim 22 wherein the plurality of fluid-handlingcomponents further comprises a filter and valve unit having a fluidinlet and a fluid outlet, wherein the filter and valve unit is removablycoupled to the control circuit and wherein the fluid outlet of thefilter and valve unit is removably coupled to the fluid inlet of thepre-concentrator.
 26. The apparatus of claim 25 wherein the plurality offluid-handling components further comprises a pump having a fluid inletand a fluid outlet, wherein the pump is removably coupled to the controlcircuit and wherein the fluid inlet of the pump is removably coupled tothe fluid outlet of the detector array.
 27. The apparatus of claim 22wherein fluid-handling assembly further comprises a shroud covering theplurality of fluid-handling components.
 28. The apparatus of claim 27wherein the shroud provides the removable coupling among the pluralityof fluid-handling components.
 29. The apparatus of claim 22 whereinfluid couplings provide the removable coupling among the plurality offluid-handling components.
 30. The apparatus of claim 19 wherein thesubstrate is a printed circuit board that includes electricalconnections that communicatively couple the control circuit to one ormore of the plurality of fluid-handling components and the readoutcircuit to the detector array.